Extra-axial inflammatory signal and its relation to peripheral and central immunity in depression

TY - JOUR

T1 - Extra-axial inflammatory signal and its relation to peripheral and central immunity in depression

AU - Eiff, Brandi

AU - Bullmore, E.T.

AU - Clatworthy, Menna

AU - Fryer, Tim

AU - Pariante, Carmine

AU - Mondelli, Valeria

AU - Maccioni, Lucia

AU - Hadjikhani, Nouchine

AU - Loggia, Marco Luciano

AU - Moskowitz, Michael A.

AU - Bruner, Emiliano

AU - Veronese, Mattia

AU - Turkheimer, Federico

AU - Schubert, Julia

PY - 2024/10/27

Y1 - 2024/10/27

N2 - Although both central and peripheral inflammation have been consistently observed in depression, the relationship between the two remains obscure. Extra-axial immune cells may play a role in mediating the connection between central and peripheral immunity. This study investigates the potential roles of calvarial bone marrow and parameningeal spaces in mediating interactions between central and peripheral immunity in depression.Positron emission tomography was employed to measure regional TSPO expression in the skull and parameninges as a marker of inflammatory activity. This measure was correlated with brain TSPO expression and peripheral cytokine concentrations in a cohort enriched for heightened peripheral and central immunity comprising 51 individuals with depression and 25 healthy controls.The findings reveal a complex relationship between regional skull TSPO expression and both peripheral and central immunity. Facial and parietal skull bone TSPO expression showed significant associations with both peripheral and central immunity. TSPO expression in the confluence of sinuses was also linked to both central and peripheral immune markers. Group dependant elevations in TSPO expression within the occipital skull bone marrow were also found to be significantly associated with central inflammation.Significant associations between immune activity within the skull, parameninges, parenchyma, and periphery highlight the role of the skull bone marrow and venous sinuses as pivotal sites for peripheral and central immune interactions.

AB - Although both central and peripheral inflammation have been consistently observed in depression, the relationship between the two remains obscure. Extra-axial immune cells may play a role in mediating the connection between central and peripheral immunity. This study investigates the potential roles of calvarial bone marrow and parameningeal spaces in mediating interactions between central and peripheral immunity in depression.Positron emission tomography was employed to measure regional TSPO expression in the skull and parameninges as a marker of inflammatory activity. This measure was correlated with brain TSPO expression and peripheral cytokine concentrations in a cohort enriched for heightened peripheral and central immunity comprising 51 individuals with depression and 25 healthy controls.The findings reveal a complex relationship between regional skull TSPO expression and both peripheral and central immunity. Facial and parietal skull bone TSPO expression showed significant associations with both peripheral and central immunity. TSPO expression in the confluence of sinuses was also linked to both central and peripheral immune markers. Group dependant elevations in TSPO expression within the occipital skull bone marrow were also found to be significantly associated with central inflammation.Significant associations between immune activity within the skull, parameninges, parenchyma, and periphery highlight the role of the skull bone marrow and venous sinuses as pivotal sites for peripheral and central immune interactions.

KW - inflammation

KW - parameninges

KW - skull

KW - microglia

KW - positron emission tomography

KW - translocator protein

U2 - 10.1093/brain/awae343

DO - 10.1093/brain/awae343

M3 - Article

SN - 1460-2156

JO - Brain

JF - Brain

ER -